EXCEED THE SPACE PROVIDED. This proposal is for the continuation of support for the 6-bed General Clinical Research Center (GCRC), its core laboratory and its outpatient research program at the Children's Hospital, Boston, the largest medical center in New England devoted to the care of children and the principal pediatric program affiliated with Harvard Medical School. Children's Hospital has 325 beds, 17,000 inpatient admissions, and 350,000 outpatient visits annually. This GCRC has a long history of clinical research innovation exemplified by the 1996 Award for Excellence in Clinical Research bestowed upon Dr. David G. Nathan, then Principal Investigator. The central mission of this GCRC is to integrate basic and clinical research, to elucidate mechanisms of disease, to formulate novel therapies and to facilitate their translation to clinical care. Our accomplishments follow this paradigm. In the past few years a pilot study of the administration of high dose corticosteroids to patients with Kawaski disease demonstrated improvement in a number of outcomes leading to a nationwide NIH funded clinical trial led by one of our investigators. Investigators characterizing the biology of ion channels have contributed to studies in sickle cell and inflammatory bowel diseases. Observations in patients with adenomas associated with glycogen storage disease, a long supported GCRC study, led to the proposed investigations into the role of hepcidin in regulating the anemia of chronic disease. Studies on the control of insulin in patients taking high and low glycemic index diets have led to a new NIH funded trial by this investigator. The investigation of infants appearing in our emergency room with hypoglycemia established that disorders in fatty acid metabolism occur in a substantial number, and should change management of such children. The Principal Investigator who is also the President and CEO of the hospital has succeeded in expanding participation of all departments in GCRC research. Among the new initiatives will be the development of a Phenotype-Genotype Core designed to extend understanding of the genetics and genetic modifiers of pediatric diseases, and the expansion of the Nutrition-Metabolism Core to develop novel therapies in response to the epidemic of obesity among children and adolescents. Substantial efforts and resources from the hospital will be directed toward attracting young investigators into clinical research. Overall, the GCRC at Children's Hospital has both initiated and responded to clinical research demands across the institution.